Heme/Onc - First Aid Flashcards
Erythrocyte Features
-carries O2 to tissues and CO2 to lungs -anucleate, biconcave -large surface area to volume ratio for rapid gas exchange -life span = 120 days -uses glucose for energy
The membrane of erythrocytes contains…
chloride-HCO3- antiporter which allows RBCs to export HCO3- and transport CO2 from the periphery to the lungs for excretion.
A reticulocyte is…
an immature erythrocyte; a marker of erythroid proliferation.
Anisocytosis
varying size
Poikilocytosis
varying shape
Platelet (thrombocyte) features
-invovled in primary hemostasis -small cytoplasmic fragment derived from megakaryocytes -life span = 8-10 days
When a platelet is activated by endothelial injury, it will…
aggregate with other platelets and interact with fibrinogen to form a platelet plug.
Platelets contain…
dens granules (ADP and calcium) and alpha granules (vWF and fibrinogen).
Thrombocytopenia or decreased platelet function results in…
petechiae.
vWF receptor
GPIb
Fibrinogen receptor
GPIIb/IIIa
Leukocytes are divided into…
granulocytes (neutrophils, eosinophils, basophils) and mononuclear cells (monocytes and lymphocytes).
Normal Leukocyte level
4000-10000
WBC differential from highest to lowest
Neutrophils Like Making Everything Better Neutrophils (54-62%) Lymphocytes (25-33%) Monocytes (3-7%) Eosinophils (1-3%) Basophils (0-.75%)
Neutrophils are…
an acute inflammatory response cell seen in bacterial infections. -phagocytic -multilobed
Small neutrophils with more numerous specific granules contain…
ALP, collagenase, lysozyme and lactoferrin.
Larger neutrophils with less numerous azurophilic granules contain…
proteinases, acid phophatase, myeloperoxidase and beta-glucoronidase.
Hypersegmented PMNs (5 or more lobes) are seen in…
vitamin B12/folate deficiency.
Increased band cells (immature neutrophils) reflect states of…
myeloid proliferation (bacterial infections, CML).
Monocytes differentiate into…
macrophages in tissues.
Monocyte features
-large, kidney-shpaed nucleus -“frosted glass” cytoplasm
Macrophages act to…
phagocytose bacteria, cellular debris and senescent RBCs and scavenge damaged cells and tissue.
Macrophages are activated from monocytes via…
gamma-interferon.
Macrophages can function as…
antigen presenting cells via MHC II.
Surface marker for macrophages
CD14
Macrophages are an important component of…
granuloma formation.
Eosinophils defend against…
helminthic infections (w/ major basic protein).
Eosinophils features
-bilobate nucleus -packed with large eosinophilic granules -highly phagocytic for Ag-Ab complexes
Eosinophils produce..
histaminase and arylsulfatase (these help limit rxn following mast cell degranulation).
Causes of eosinophilia
NAACP N: neoplasia A: asthma A: allergies C: CT disorders P: parasites
Basophils mediate…
allergic rxns.
Basophil features
densely basophilic granules containing heparin (anticoagulant), histamine (vasodilator) and leukotrienes.
Isolated basophilia is rare but can be a sign of…
myeloproliferative disease (particularly CML).
Mast cells mediate…
allergic rxn in local tissue. (resemble basophils)
Mast cells can bind…
the Fc portion of IgE to the membrane. IgE cross-links upon Ag binding, causing degranulation, which releases heparin, histamine, and eosinophilic chemotactic factors.
Mast cells are involved in…
type I HSR.
Mast cell degranulation is prevented by…
cromolyn sodium (used for asthma prophylaxis).
Dendritic cells are…
highly phagocytic APCs that function as the link between the innate and adaptive immune systems.
Dendritic cells express…
MHC class II and Fc receptors on the surface.
Dendritic cells of the skin are called…
Langerhans cells.
Lymphocyte appearance
round, densely staining nucleus with a small amount of pale cytoplasm
B lymphocytes arise from…
stem cells in bone marrow, mature there and then migrate to peripheral lymphoid tissue (follicles of LNs, white pulp of spleen).
When Ag is encountered, B cells will…
differentiate into plasma cells that produce Abs and memory cells.
B cells can function as…
an APC via MHC II.
T lymphocytes originate from…
stem cells in the bone marrow but mature in the thymus.
The costimulatory signal necessary for T-cell activation is…
CD28.
The primary target of HIV is…
CD4+ helper T cells.
Plasma cell appearance
eccentric nucleus clock-face chromatin abundant RER well-developed Golgi apparatus
Universal recipient of RBCs
AB blood group
Universal donor of plasma
AB blood group
Universal donor of RBCs
O blood group
Universal recipient of plasma
O blood group
Rh- mothers who are exposed to fetal Rh+ blood (oftenduring delivery) may make…
anti-Rh IgG. In subsequent pregnancies, anti-Rh IgG crosses the placenta causing hemolytic disease of the newborn (erythroblastosis fetalis).
Rho(D) immune globulin is given for…
mothers during every pregnancy to prevent intial sensitizaiton of Rh- mother to Rh antigen.
Warfarin acts by…
inhibiting the enzyme vitamin K epoxide reductase to prevent maturation of coagulation factors.
Neonates lack enteric bacteria which produce…
vitamin K.
Vitamin K deficiency leads to…
decreasd synthesis of factors II, VII, IX, X, protein C and S.
vWF carries/protects…
factor VIII.
Antithrombin inhibits…
activated forms of factors II, VII, IX, X, XI, XII.
Heparin enhances…
the activity of antithrombin.
Principal targets of antithrombin
thrombin and factor Xa
Factor V Leiden mutation produces…
a factor V resistant to inhibition by activated protein C.
tPA is used clinically as…
a thrombolytic. It converts plasminogen to plasmin which then causes fibrinolysis.
A normal platelet aggregation response is not seen in…
von Willebrand disease.
Acute phase reactants in plasma (fibrinogen) can cause…
RBC aggregation, thereby increasing RBC sedimentation rate.
Increased ESR (erythrocyte sedimentation rate) is seen in…
infxns autoimmune diseases malignant neoplasms GI disease (UC) pregnancy
Decreased ESR is seen in…
polycythemia sickle cell anemia CHF microcytosis hypofibrinogenemia
Acanthocyte (spur cell)
-liver disease -abetalipoproteinemia (states of cholesterol dysregulation)
Basophilic stippling
-anemia of chronic disease -alcohol abuse -lead poisoning -thalassemias
Bite cell
G6PD deficiency
Elliptocyte
Hereditary elliptocytosis
Macro-ovalocyte
megaloblastic anemia (also hypersegmented PMNs) marrow failure
Ringed sideroblast
sideroblastic anemia (excess iron in mitochondria)
Schistocyte/helmet cell
DIC TTP/HUS traumatic hemolysis (mechanical heart valve prosthesis)
Spherocyte
hereditary spherocytosis autoimmune hemolysis
Teradrop cell
bone marrow infiltration (myelofibrosis) *RBCs shed a tear bc they have been forced out of their home in the bone marrow.
Target cells
HbC disease Asplenia Liver disease Thalassemia
Heinz bodies are seen in…
G6PD deficiency; Heinz body-like inclusions are seen in alpha-thalassemia.
Heinz bodies cause….
oxidation of Hb sulfhydryl groups leading to denatured Hb precipitation and phagocytic damage to the RBC membrane forming bite cells.
Heinz bodies are visualized with…
special stains such as crystal violet.
Howell-Jolly bodies are seen in pts with…
functionl hyposplenia or asplenia.
Howell-Jolly bodies are…
basophilic nuclear remnants found in RBCs. They are normally removed from RBCs by splenic macrophages.
Iron deficiency can be caused by…
chronic bleeding, malnutrition/absorption disorders, pregnancy
Iron deficiency decreases…
the final step in heme synthesis leading to a microcytic, hypochromic anemia.
Findings in Iron Deficiency Anemia
-decreased iron -increased TIBC -decreased ferritin -fatigue -conjunctival pallor
Iron Deficiency Anemia may manifest as…
Plummer-Vinson syndrome which is a triad of: 1. iron deficiency anemia 2. esophageal webs 3. atrophic glossitis
alpha-thalassemia has a defect in…
alpha-globin gene (deletions) leading to decreased synthesis.
cis alpha-thalassemia deletion is prevalent in…
Asian populations. The trans deletion is prevalent in African populations.
alpha-thalassemia (4 allele deletion):
-no alpha-globin -excess gamma globin forms gamma4 (Hb Barts) -incompatible with life (hydrops fetalis)
alpha-thalassemia (3 allele deletion):
-HbH diseae -very little alpha globin -excess beta-globin forms beta4 (HbH)
alpha-thalassemia (1-2 allele deletion):
no clinically significant anemia
Beta-thalassemia is…
a microcytic, hypochrmoic anemia due to point mutations in splice sites and promoter sites leading to decreased beta-globin synthesis; prevalent in mediterranean populations
Beta-thalassemia minor (heterozygote) features
-beta chain underproduced -usually asymptomatic -diagnosis confirmed by increased HbA2 (> 3.5%) on electrophoresis
Beta-thalassemia major (homozygote) features
-beta chain absent (severe anemia requiring blood transfusion) -marrow expansion (“crew cut” on skull x-ray) leading to skeletal deformities (chipmunk facies) -extramedullary hematopoiesis (hepatosplenomegaly)
Beta-thalassemia major pts are at increased risk for…
parvovirus B-19 induced aplastic crisis.
Beta-thalassemia major has increased…
HbF which is protective for the 1st 6 months of life (no symptoms).
HbS/beta-thalassemia heterozygote
mild/moderate sickle cell depending on amount of beta-globin production
Lead inhibits…
ferrochelatase and ALA dehydratase leading to decreased heme synthesis and increased RBC protoprophyrin;
Lead also inhibits…
rRNA degradation causing RBCs to retain aggregates of rRNA (basophilic stippling).
High risk of lead poisoning in…
old houses with chipped paint.
Lead poisoning findings
-lead lines on gingivae and long bones -encephalopathy -erythocyte basophilic stippling -abdominal colic -sideroblastic anemia -wrist and foot drop
1st line treatment for lead poisoning is…
Dimercaprol and EDTA.
In kids with lead poisoning, treatment is…
Succimer for chelation. (It SUCks to be a kid who eats lead.)
Sideroblastic Anemia is due to…
a defect in heme synthesis.
Hereditary sideroblastic anemia
X-linked defect in delta-ALA synthase gene
Causes of sideroblastic anemia
-genetic -acquired -alcohol -lead -vitamin B6 deficiency -copper deficiency -isoniazid
Sideroblastic Anemia presents with
-increased iron -normal TIBC -increased ferriting -ringed sideroblasts (w/ iron-laden mitochondria)
Treatment for sideroblastic anemia
pyridoxine (B6 - cofactor for delta-ALA synthase)
Megaloblastic anemia is due to…
impaired DNA synthesis. This causes the maturation of the nucleus of precursor cells in bone marrow to be delayed relative to the maturation of the cytoplasm. This causes abnormal cell division leading to pancytopenia.
3 types of megaloblastic anemia
-folate deficiency -B12 deficiency -orotic aciduria
Causes of folate deficiency megaloblastic anemia
-malnutrition (alcoholics) -malabsorption -anifolates (methotrexate, trimethoprim, phenytoin) -increased requirement (hemolytic anemia, pregnancy)
Findings of Folate deficiency
-hypersegmented neutrophils -glossitis -decreased folate -increased homocysteine but normal methylmalonic acid -NO neuro symptoms (distinguishes from B12 deficiency)
Causes of B12 deficiency anemia
-insufficient intake (vegans) -malabsorption -pernicious anemia -Diphyllobothrium latum -proton pump inhibitors
Findings of B12 Deficiency
-hypersegmented neutrophils -glossitis -decreased B12 -increased homocysteine -increased methylmalonic acid -neuro symptoms
Neurologic symptoms of B12 deficiency are due to..
subacute combined degeneration due to involvement of B12 in fatty acid pathways and myelin synthesis.
Neuro symptoms of B12 Deficiency
- peripheral neuropathy w/ sensorimotor dysfunction 2. dorsal columns (vibration/proprioception) 3. lateral corticospinal (spasticity) 4. dementia
Orotic aciduria is due to…
the inability to convert orotic acid to UMP because of a defect in UMP synthase.
Orotic aciduria presents in…
children as megalobastic anemia that cannot be cured by folate or B12 with FTT.
Orotic aciduria does not have…
hyperammonemia (which distinguishes it from ornithine transcarbamylase deficiency).
Findings of Orotic Aciduria
-hypersegmented neutrophils -glossitis -orotic acid in urine
Treatment for Orotic Aciduria
uridine monophosphate to bypass the mutated enzyme
Causes of nonmegaloblatic, macrocytic anemia
-liver disease -alcoholism -reticulocytosis -drugs (5-FU, zidovudine, hydroxyurea)
Findings of nonmegaloblastic, macrocytic anemias
macrocytosis bone marrow suppression
Normocytic, normochromic anemias are classified as either…
hemolytic or nonhemolytic.
Findings of Intravascular Hemolysis
-decreased haptoglobin -increaesed LDH -schistocytes -increased reticulocytes -urobilinogen in the urine
Finings of Extravascular Hemolysis
-macrophages in the spleen clear RBCs -spherocytes -increased LDH -increased unconjugated bilirubin
Nonhemolytic, hormocytic anemias (3)
- anemia of chronic disease 2. aplastic anemia 3. chronic kidney disease
In Anemia of Chronic Disease, inflammation leads to..
increased hepcidin (released by the liver, binds ferroportin on intestinal mucosal cells, thus inhibiting iron transport) leading to decreased release of iron from macrophages.
Findings of Anemia of Chronic Disease
-decreased iron -decreased TIBC -increased ferritin
Aplastic anemia is caused by…
failure or destruction of myeloid stem cells due to: -radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites) -viral agents (parvovirus B19, EBV, HIV, HCV) -Fanconi anemia -
Findings of Aplastic Anemia
-pancytopenia characterized by severe anemia, leukopenia and thrombocytopenia -normal cell morphology -hypocellular bone marrow with fatty infilration (dry bonemarrow tap)
Symptoms of Aplastic Anemia
-fatigue -malaise -purpura -mucosal bleeding -petechiae -infxn
Treatment of aplastic anemia
-immunosuppressive regimens -allogeneic bone marrow transplant -RBC/platelet transfusion -G-CSF -GM-CSF
Chronic kidney disease causes anemia because…
decreaed EPO leads to decreased hematopoiesis.
Types of Intrinsic Hemolytic Normocytic Anemia
-Hereditary spherocytosis (E) -G6PD deficiency (I/E) -Pyruvate kinase deficiency (E) -HbC defect (E) -Paroxysmal nocturnal hemoglobinuria (I) -Sickle Cell Anemia (E)
Hereditary spherocytosis is due to a defect in…
proteins interacting with RBC membrane skeleton and plasma membrane (ankyrin, band 3, protein 4.2, spectrin)
In hereditary spherocytosis, less membrane causes…
small and round RBCs with no central pallor (increased MCHC and increased red cell distribution width) leading to premature removal of RBCs by the spleen.
Findings in hereditary spherocytosis
-splenomegaly -aplastic crisis (w/ parvovirus B19 infxn)
Labs of Hereditary spherocytosis
-osmotic fragility test positive -eosin-5-maleimide binding test useful for screening -normal/decreased MCV with abundance of cells
Hereditary spherocytosis masks…
microcytia.
Treatment for hereditary spherocytosis
splenectomy
The most common enzymatic disorder of RBCs is…
G6PD deficiency (X-linked).
In G6PD deficiency, a defect in G6PD leads to…
decreased glutathione leading to increased RBC susceptibility to oxidant stress. Then there is hemolytic anemia followng oxidant stress.
In G6PD deficiency, classic causes of oxidant stress are…
sulfa drugs, antimalarials, infxns, fava beans.
Findings of G6PD deficiency
-back pain -hemoglobinuria a few days after oxidant stress
Labs for G6PD deficiency
RBCs with Heniz bodies and bite cells
Pyruvate kinase deficiency has a defect in…
pyruvate kinase which leads to decreased ATP and rigid RBCs.
Pyruvate kinase deficiency presents as…
hemolytic anemia in a newborn.
HbC defect is due to a…
glutamic acid to lysine mutation at residue 6 in the beta-globin.
HbC defect pts with HbSC (1 of each mutant gene) have…
milder disease than HbSS pts have.
Paroxysmal nocturnal hemoglobinuria is an…
acquired mutation in a hematopoietic stem cell leading to increased complement-mediated RBC lysis (there is impaired synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement).
Paroxysmal nocturnal hemoglobinuria has increased incidence of…
acute leukemias.
Triad of Paroxysmal nocturnal hemoglobinuria
-Coombs negative hemolytic anemia -pancytopenia -venous thrombosis
Labs for Paroxysmal Nocturanl Hemoglobinuria
-CD55/59 negative RBCs on flow cytometry
Treatment for Paroxysmal Nocturnal Hemoglobinuria
Eculizumab
Sickle Cell Anemia has a…
HbS point mutation that causes a single amino acid replacement in the beta-chain (substitution of gluatmic acid with valine) at position 6.
Pathogenesis of Sickle Cell Anemia
low O2, dehydration or acidosis preciptates sickling (deoxygenated HbS polymerizes) which results in amemia and vaso-occlusive disease
Newborns with sickle cell are initially…
asymptomatic because of increased HbF and decreased HbS.
Heterozygotes (sickle cell trait) have…
resistance to malaria.
On skull x-ray, sickle cell shows…
“crew cut” due to marrow expansion from increased erythropoiesis (also in thalassemias).
Complications in sickle cell
-aplastic crisis (due to parvovirus B19) -autosplenectomy (increased risk of infxn with encapsulated organisms) -splenic sequestration crisis -salmonella osteomyelitis -dactylitis (painful hand swelling) -acute chest syndrome -avascular necrosis -stroke -renal papillary necrosis -microhematuria
Diagnosis of sickle cell is made with…
hemoglobin electrophoresis
Treatment of sickle cells
hydroxyurea (increases HbF) bone marrow transplant
Extrinsic Hemolytic normocytic anemias
- autoimmune hemolytic anemia 2. microangiopathic anemia 3. macroangiopathic anemia 4. infxn
Autoimmune hemolytic anemia with warm agglutinin is…
chronic anemia seen in SLE, CLL or with certain drugs (alpha-methyldopa). IgG mediated.
Autoimmune hemolytic anemia (AIHA) with cold agglutinin is seen with…
acute anemia triggered by cold; seen in CLL, mycoplasma penumonia infections or infectious mononucleosis
AIHAs are usually positive for…
Coombs.
Direct Coombs Test
anti-Ig antibody added to pts blood; RBCs agglutinate if RBCs are coated with Ig
Indirect Coombs Test
normal RBCs added to pts serum; if serum has anti-RBC surface Ig, RBCs agglutinate when anti-Ig antibodies are added.
Microangiopathic anemia pathogenesis
RBCs are damaged when passing through obstructed or narrowed vessel lumina
Microangiopathic anemia is seen in…
DIC, TTP-HUS, SLE and malignant HTN.
On blood smear of microangiopathic anemia, there are…
schistocytes (helmet cells) due to mechanical destruction of RBCs.
Macroangiopathic anemia is due to…
prosthetic heart valves and aortic stenosis secondary to mechanical damage. Show schistocytes.
Infections can increase the…
destruction of RBCs (malaria, Babesia).
Transferrin
transports iron in the blood
Ferritin
primary iron storage protein of the body
Neutropenia definition
absolute neutrophil count < 1500
Neutropenia causes
-sepsis/postinfection -drugs -aplastic anemia -SLE -radiation
Lymphopenia definition
absolute lymphocyte count < 1500
Causes of lymphopenia
-HIV -DiGeorge syndrome -SCID -SLE -corticosteroids -radiation -sepsis -postoperative
Eosinopenia causes
-cushing syndrome -corticosteroids
Corticosteroids cause neutrophilia because they…
decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation.
Corticosteroids cause eosinopenia and lymphopenia becasue they…
sequester eosinophils in LNs and cause apoptosis of lymphocytes.
The porphyrias are…
conditions of defective heme synthesis that lead to accumulation of heme precursor. (lead inhibits enzymes of heme synthesis, leading to similar conditions)
Affected enzyme in lead poisoning
-ferrochelatase -ALA dehydratase
Accumulated substrate in lead posioning
-protoporphyrin -delta-ALA (in blood)
Presenting symptoms of Lead poisoning
-microcytic anemia -GI/kidney disease
Common presentation of lead poisoning in children
Exposure to lead point leads to mental deterioration.
Common presentation of lead poisoning in adults
environmental exposure (battery/ammunition/radiator factory) leads to HA, memory loss, demyelination)
Affected enzyme in acute intermittent porphyria
porphobilinogen deaminase
Accumulated substrate in acute intermittent porphyria
-porphobilinogen -delta-ALA -coporphobilinogen (urine)
Presenting symptoms of acute intermittent porphyria
-painful abdomen -port-wine colored urine -polyneuropathy -pscyhological disorders -precipitated by drugs, alcohol and starvation (5 Ps)
Treatment for acute intermittent porphyria
-glucose and heme (which inhibit ALA synthase)
Affected enzyme in Porphyria cutanea tarda
uroporphyrinogen decarboxylase
Accumulated substrate in Porphyria cutanea tarda
uroporphyrin (tea-colored urine)
Presenting symptom of Porphyria cutanea tarda
blistering cutaneous photosensitivity tea-colored urine
Prothrombin Time (PT) tests…
the function of the common and extrinsic pathway (factors I, II, V, VII, and X); a defect will increase PT.
PTT tests…
function of common and intrinsic pathway (all factors exceptr VII and XIII); defect will increase PTT.
Hemophilia A features
-increased PTT -deficiency of factor VIII
Hemophilia B features
-increased PTT -deficiency of factor IX
Clinical findings of Hemophilia A and B
-hemarthroses (bleeding into joints) -easy bruising
Treatment for Hemophilia A
-recmobinant factor VIII
Vitamin K deficiency features
-increased PT -increased PTT -bleeding time is normal -decreased synthesis of factors II, VII, IX, X, protein C and protein S
Defects in platelet plug formation leads to…
increased bleeding time
Platelet abnormalities lead to…
microhemorrhage: mucous membrane bleeding (epistaxis), petechiae/purpura, increased bleeding time, decreased platelet count
Bernard-Soulier Syndrome Featuers
-increaed bleeding time -decreased platelets -decreased GpIb (leads to defect in platelet to vWF adhesion)
Glanzmann thrombasthenia features
-increased bleeding time -decreased GpIIb/IIIa (defect in platelet to platelet aggregation) -blood smear shows no platelet clumping
Immune thrombocytopenia
-decreased platelets -increased bleeding time -anti-GpIIb/IIIa antibodies (splenic macrophage consumes platelet/Ab complex) -may be triggered by viral illness -increased megakaryocytes on bone marrow biopsy
Thrombotic thrombocytopenic pupura (TTP) features
-decreased platelets -increased bleeding time -deficiency of ADAMTS 13 leads to decreased degradation of vWF multimers
In TTP, with the increased large vWF multimers, it leads to…
increased platelet adhesion and increased platelet aggregation and thrombosis.
Labs of TTP
schistocytes, increased LDH
Symptoms of TTP
-pentad of neurologic and renal symptoms, fever, thrombocytopenia and microangiopathic hemolytic anemia (FATRN)
Treatment for TTP
exchange transfusion and steroids
von Willebrand Disease features
-increased bleeding time -normal/increased PTT -decreased vWF causes a defect in platelet-to-vWF adhesion
Characteristics of von Willebrand Disease
-mild -autosomal dominant
Diagnose von Willebrand Disease with…
ristocetin cofactor assay (decreased agglutination is diagonistic).
Treatment for von Willebrand Disease
DDAVP (desmopressin) which releases vWF stored in endothelium
DIC features
-decreased platelets -increased bleeding time -increased PT -increased PTT
DIC is…
widespread activation of clotting which leads to a deficiency in clotting factors which creates a bleeding state.
Causes of DIC
Sepsis (gram-negative) Trauma Obstetric complications acute Pancreatitis Malignancy Nephrotic syndrome Transfusion (STOP Making New Thrombi)
Labs for DIC
-schistocytes -increased fibrin split products (D-dimers) -decreased fibrinogen -decreased factors V and VIII
vWF acts to…
carry/protect factor VIII
Factor V Leiden is production of…
mutatn factor V that is resistant to degradation by activated protein C.
Hereditary thrombosis sydnromes leading to hypercoaguability
- Factor V Leiden 2. Prothrombin gene mutation 3. Antithrombin deficiency 4. Protein C or S deficiency
Prothrombin Gene Mutation is in the…
3’ untranslated region leading to increased production of prothrombin leading to venous clots.
Antithrombin deficiency is inherited and has no direct effect on…
PT, PTT or thrombin time but diminshes the increase in PTT following heparin administration.
Antithrombin deficiency can also be acquired when…
renal failure leads to antithrombin loss in the urine leading to increased factors II and X.
Protein C or S deficiency leads to decreased ability to…
inactivate factors V and VIII leading to increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin.
Packed RBCs effect
increase Hb and O2 carrying capacity
Packed RBCs clinical use
acute blood loss severe anemia
Platelets transfusion clinical use
stop significant bleeding (thrombocytopenia)
Fresh frozen plasma transfusion effect
increase coagulation factors
FFP transfusion clinical use
DIC cirrhosis warfarin overdose exchange transfusion in TTP/HUS
Cryoprecipitate transfusion effect
contains fibrinogen, factor VIII, factor XIII, vWF and fibronectin
Clincial use of cryoprecipitate transfusion
treat coagulation factor deficiencies involving fibrinogen and factor VIII
Blood transfusion risks include..
infection transmission transfuscion reactions iron overload hypocalcemia hyperkalemia
Leukemia
lymphoi or myeloid neoplasms with widespread involvement of bone marrow; tumor cells are usually found in peripheral blood
Lymphoma
discrete tumor masses arising from LNs
Leukemoid rxn is an…
acute inflammatory response to infection.
Features of the Leukemoid Reaction
-increased WBC -increased neutrophils and band cells -increased leukocyte ALP
Hodgkin Lymphoma
localized, single group of nodes; extranodal is rare; contiguous spread; better prognosis
Hodgkin Lymphoma is characterized by…
Reed-Sternberg cells.
Distribution of Hodgkin Lymphoma is…
bimodal: young adulthood and greater than 55. Usually in men.
50% of Hodgkin Lymphoma is associated with…
EBV.
Symptoms of Hodgkin’s
-contitutional (B) symptoms - low fever, night sweats, weight loss
Non-Hodgkin lymphoma
-multiple, peripheral nodes -extranodal involvement common -noncontiguous spread
The majority of Non-Hodgkin lymphomas involve…
B cells.
Peak incidence for Non-Hodgkin’s is…
20-40.
Non-Hodgkin’s lymphom may be associated with…
HIV and immunosuppression.
Reed-Sternberg cells
-binucleate -CD15 and CD30 + -B cell origin -necessary for diagnosis of Hodgkin Lymphoma
Forms of Hodgkin lymphoma
-nodular sclerosing form most common -lymphocyte-rich has best prognosis
Neoplasms of mature B cells (Non-Hodgkin lymphomas)
- Burkitt 2. Diffuse large B-cell 3. Mantle Cell 4. Follicular
Burkitt lymphoma occurs in…
adolescents.
Burkitt lymphoma genetics
t(8;14) translocation of c-myc and heavy-chain Ig
Histology of Burkitt
-“starry sky” appearance -sheets of lymphocytes w/ interspersed macrophages
Burkitt is associated with…
EBV
Different forms of Burkitt
Endemic form: jaw lesion, Africa Sporadic form: pelvis or abdomen
Diffuse large B-cell lymphoma (DLBL) occurs in…
older adults usually.
Genetics of Diffuse large B-cell lymphoma
t(14;18)
Mantle cell lymphoma occurs in…
older males.
Mantle cell lymphoma genetics
t(11;14) translocation of cyclin D1 and heavy chain Ig
Mantle cell lymphoma cell marker
CD5+
Follicular lymphoma is seen in…
adults.
Genetics of follicular lymphoma
t(14;18) translocation of heavy chain Ig and bcl-2
bcl-2 inhibits…
apoptosis.
Follicular lymphoma presents with…
painless “waxing and waning” lymphadenopathy.
Neoplasms of mature T cells (non-hodgkin lymphoma)
*see cutaneous lesions in adults 1. Adult T-cell lymphoma 2. Mycosis fungoides/Sezary syndrome
Adult T-cell lymphoma is caused by…
HTLV-1 and is associated with IV drug abuse.
Presentation of Adult T-cell lymphoma
-cutaneous lesions -esp. in Japan, West Africa and Caribbean -lytic bone lesions and hypercalcemia
Presentation of Mycosis fungoides/Sezary syndrome
-adults present with cutaneous patches/plaques/tumors with potential to spread to LNs and viscera -circulating malignant cells -CD4+
Multiple myeloma is a…
monoclonal plasma cell (“fried egg” appearance) cancer that arises in the marrow and produces large amounts of IgG and IgA.
Multiple myeloma is associated with…
-increased susceptiblity to infection -primary amyloidosis -punched out lytic bone lesions -M spike on serum protein electrophoresis -Ig light chains in urine (Bence Jones protein) -Rouleaux formation (stacked RBCs)
Histology of Multiple myeloma
-numerous plasma cells with “clock face” chromatin -intracytoplasmic inclusions containing Ig
Waldenstrom macroglobulinemia is similar to Multiple myeloma except…
M spike is from IgM and there are no lytic bone lesions.
Monoclonal gammopathy of undetermined significance (MGUS)
monoclonal expansion of plasma cells with M spike and decreased plamsa cells in bone marrow **asymptomatic precursor to multiple myeloma
Myelodysplastic syndromes are…
stem cell disorders involving ineffective hematopoiesis leading to defects in cell maturation of all non-lymphoid lineages.
Myelodysplastic syndromes are caused by…
de novo mutations or environmental exposure (radiation, benzene, chemo).
Myelodysplastic syndrome has a risk of trasnformation to..
AML.
Pseudo-Pelger-Huet anomaly
neutrophils with bilobed nuclei typically seen after chemo
Acute lymphoblastic leukemia/lymphoma (ALL) is seen in those…
less than 15.
T-cell ALL can present as a…
mediastinal mass (leukemic infiltration of the thymus).
ALL is associated with…
Down Syndrome.
Markers of ALL
-increased lymphoblasts in blood and marrow -TdT+ -CD10+
ALL other features
-responsive to therapy -may spread to CNS and testes -t(12;21) = better prognosis
In leukemias, unregulated growth of…
leukocytes in bone marrow leads to anemia, infxns and hemorrhage.
Small lymphocytic lymphoma or Chronic lymphocytic lymphoma (SLL/CLL) features
-age > 60 yrs -CD20+ -CD5+ -B cells -progresses slowly -smudge cells -AIHA
SLL is the same as CLL except CLL has…
increased peripheral blood lymphocytosis or bone marrow invovlement.
Hairy Cell Leukemia features
-adults -B cells -cells have filamentous, hair-like projections
Hairy cell leukemia stains…
TRAP positive.
Hairy cell leukemia causes…
marrow fibrosis (dry tap).
Treatment for Hairy cell
-cladribine (an adenosine analog that inhibits adenosine deaminase)
Acute myelogenous leukemia (AML) features
-65 yrs -auer rods -peroxidase + -increased circulating myeloblasts
Risk factors for AML
-alkylating chemo -radiation -myeloproliferative disorders -down syndrome
M3 type of AML has…
a t(15;17) translocation.
M3 subtype of AML responds to…
all trans retinoic acid (vitamin A) which induces differentiation of myeloblasts.
Common presentation of AML is…
DIC which is induced by chemo due to release of Auer rods.
Chronic myelogenous leukemia (CML)
-45-85 yrs -philadelphia chromosome t(9;22) - bcr-abl -myeloid stem cell proliferation -increased neutrophils, metamyeloctyes and basophils -splenomegaly
CML may progress to…
AML or ALL (“blast crisis”).
As a result of low activity in the granulocytes, CML has a very low level of…
leukocyte alkaline phosphatase.
CML responds to…
imatinib (an inhibitor of the bcr-abl tyrosine kinase).
Langerhans cell histiocytosis is a proliferative disorder of…
dendritic cells from a monocyte lineage that presents in a child as lytic bone lesions and skin rash. Or recurrent otitis media with a mass involving the mastoid bone.
In langerhans cell histiocytosis, the cells are…
functionally immature and do not efficiently stimulate the primary T lymphocytes via Ag presentation.
Langerhans cell histiocytosis cells express…
S-100 (mesodermal origin) and CD1a. Birbeck granules (tennis rackets) are characteristic.
Polycythemia vera features
-hematocrit > 55% -mutation in JAK2
Polycythemia vera presents as…
intense itching after hot shower. Classic symptom is erythromelalgia (severe, burning pain and red/blue color) due to episodic clots in extremities.
Secondary polycythemia is via…
natural or artificial increase in EPO.
Essential thrombocytosis is similar to polycythemia vera but is specific for…
overproduction of abnormal platelets leading to… bleedign and thrombosis. The bone marrow contains enlarged megakaryocytes.
Myelofibrosis is…
fibrotic obliteration of the bone marrow. Teardrop RBCs and immature forms of the myeloid line are seen.
bcr-abl transformation in CML leads to…
increased cell division and inhibition of apoptosis.
